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Synj2bp 在小鼠肝脏中的表达调节了网膜蛋白-线粒体接触的程度，以维持肝内脂质的动态平衡。

Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis.

机构信息

Graduate Program in Neuroscience, Faculty of Medicine, Laval University, Quebec, QC, Canada.

Mitochondria Biology Laboratory, Brain Research Center, Laval University, Quebec, QC, Canada.

出版信息

Biol Direct. 2022 Dec 1;17(1):37. doi: 10.1186/s13062-022-00344-8.

DOI:10.1186/s13062-022-00344-8
PMID:36457006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9717519/
Abstract

BACKGROUND

In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142-143, 2021; Ilacqua et al. in J Cell Sci 135:1-11, 2021). A disruption of the ultrastructure of the wrappER-mitochondria contact results in altered fatty acid flux, leading to hepatic dyslipidemia (Anastasia et al. 2021). The molecular mechanism that regulates the extent of wrappER-mitochondria contacts is unknown.

METHODS

We evaluated the expression level of the mitochondrial protein Synj2bp in the liver of normal and obese (ob/ob) mice. In addition, we silenced its expression in the liver using an AAV8 vector. We coupled quantitative EM morphometric analysis to proteomics and lipid analyses on these livers.

RESULTS

The expression level of Synj2bp in the liver positively correlates with the extent of wrappER-mitochondria contacts. A 50% reduction in wrappER-mitochondria contacts causes hepatic dyslipidemia, characterized by a gross accumulation of lipid droplets in the liver, an increased hepatic secretion of VLDL and triglycerides, a curtailed ApoE expression, and an increased capacity of mitochondrial fatty acid respiration.

CONCLUSION

Synj2bp regulates the extent of wrappER-mitochondria contacts in the liver, thus contributing to the control of hepatic lipid flux.

摘要

背景

在小鼠肝实质细胞中，每个线粒体的近一半表面积都被_WRAPPER_覆盖，_WRAPPER_是一种富含脂肪酸并合成脂蛋白（VLDL）的包绕型内质网（Anastasia 等人，Cell Rep 34：108873，2021；Hurtley，Science（80- ）372：142-143，2021；Ilacqua 等人，J Cell Sci 135：1-11，2021）。_WRAPPER- 线粒体接触的超微结构破坏会导致脂肪酸通量改变，从而导致肝脂质代谢紊乱（Anastasia 等人，2021）。调节_WRAPPER- 线粒体接触程度的分子机制尚不清楚。

方法

我们评估了正常和肥胖（ob/ob）小鼠肝脏中线粒体蛋白 Synj2bp 的表达水平。此外，我们使用 AAV8 载体在肝脏中沉默其表达。我们将定量 EM 形态计量分析与这些肝脏的蛋白质组学和脂质分析相结合。

结果

Synj2bp 在肝脏中的表达水平与_WRAPPER- 线粒体接触的程度呈正相关。_WRAPPER- 线粒体接触减少 50%会导致肝脂质代谢紊乱，其特征是肝脏中脂质滴大量积累、VLDL 和甘油三酯的肝分泌增加、ApoE 表达减少以及线粒体脂肪酸呼吸能力增加。

结论

Synj2bp 调节肝脏中_WRAPPER- 线粒体接触的程度，从而有助于控制肝内脂质通量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/001ebf6aff29/13062_2022_344_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/c4b038e58e25/13062_2022_344_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/9a75adf96d05/13062_2022_344_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/78b9c10dc0a1/13062_2022_344_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/02170d46526a/13062_2022_344_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/619c0fc599cb/13062_2022_344_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/001ebf6aff29/13062_2022_344_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/c4b038e58e25/13062_2022_344_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/9a75adf96d05/13062_2022_344_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/78b9c10dc0a1/13062_2022_344_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/02170d46526a/13062_2022_344_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/619c0fc599cb/13062_2022_344_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea88/9717519/001ebf6aff29/13062_2022_344_Fig6_HTML.jpg

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